Efficacy and Safety of Interleukin-12/23 and Interleukin-23 Inhibitors for Ulcerative Colitis: A Systematic Review Ad Meta-Analysis of Randomized Controlled Trials.
Fouad Jaber, Mohammed Ayyad, Saqr Alsakarneh, Tala Alsharaeh, Ahmed-Jordan Salahat, Mohammad Jaber, Manesh Kumar Gangwani, Yazan Abboud, Islam Mohamed, Hassam Ali, Yassine Kilani, Francis A Farraye, Jana G Hashash
{"title":"Efficacy and Safety of Interleukin-12/23 and Interleukin-23 Inhibitors for Ulcerative Colitis: A Systematic Review Ad Meta-Analysis of Randomized Controlled Trials.","authors":"Fouad Jaber, Mohammed Ayyad, Saqr Alsakarneh, Tala Alsharaeh, Ahmed-Jordan Salahat, Mohammad Jaber, Manesh Kumar Gangwani, Yazan Abboud, Islam Mohamed, Hassam Ali, Yassine Kilani, Francis A Farraye, Jana G Hashash","doi":"10.1097/MJT.0000000000001766","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Targeting interleukin-23 (IL-23) represents a significant therapeutic avenue for treating ulcerative colitis (UC).</p><p><strong>Study question: </strong>What are the effectiveness and safety of selective inhibitors targeting IL-23p19 and IL-12/23p40 in individuals with moderate-to-severe UC?</p><p><strong>Data sources: </strong>MEDLINE, Embase, Scopus, and Cochrane databases.</p><p><strong>Study design: </strong>A systematic search of MEDLINE, Embase, Scopus, and Cochrane databases till January 15, 2024, to identify randomized controlled trials comparing IL-23p19 and IL-12/23p40 inhibitors against placebo or active comparators in UC patients. The primary outcome was clinical remission, with secondary outcomes including clinical response, endoscopic remission, and safety profiles during induction and maintenance phases. Using a fixed-effect model, we pooled dichotomous data with risk ratio (RR) and 95% confidence interval (CI) for analysis.</p><p><strong>Results: </strong>In 5 trials involving 1120 patients with moderate to severe UC, targeting IL-23 showed significant superiority in inducing clinical remission [RR: 2.08, 95% CI, (1.66-2.61)], endoscopic remission [RR: 1.73, 95% CI, (1.39-2.16)], and histologic remission [RR: 1.88, 95% CI, (1.34-2.64)]. Additionally, individuals treated with IL-12/23p40 or IL-23p19 antagonists maintained clinical remission [RR: 1.85, 95% CI, (1.53-2.23)], endoscopic remission [RR: 2.03, 95% CI, (1.60-2.57)], and histologic remission [RR: 1.66, 95% CI, (1.11-2.48)]. Targeting IL-23 was linked with a reduced risk of any adverse events (AE) during both induction [RR: 0.94, 95% CI, (0.86-1.02)] and maintenance phases [RR: 0.93, 95% CI, (0.86-0.99)], any serious AE during the induction phase [RR: 0.53, 95% CI, (0.36-0.78)], and withdrawal due to AEs compared to patients receiving placebo during induction [RR: 0.24, 95% CI (0.14, 0.43)].</p><p><strong>Conclusion: </strong>Targeting IL-23 demonstrates efficacy and safety for inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC patients.</p>","PeriodicalId":7760,"journal":{"name":"American journal of therapeutics","volume":" ","pages":""},"PeriodicalIF":2.9000,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of therapeutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/MJT.0000000000001766","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Targeting interleukin-23 (IL-23) represents a significant therapeutic avenue for treating ulcerative colitis (UC).
Study question: What are the effectiveness and safety of selective inhibitors targeting IL-23p19 and IL-12/23p40 in individuals with moderate-to-severe UC?
Data sources: MEDLINE, Embase, Scopus, and Cochrane databases.
Study design: A systematic search of MEDLINE, Embase, Scopus, and Cochrane databases till January 15, 2024, to identify randomized controlled trials comparing IL-23p19 and IL-12/23p40 inhibitors against placebo or active comparators in UC patients. The primary outcome was clinical remission, with secondary outcomes including clinical response, endoscopic remission, and safety profiles during induction and maintenance phases. Using a fixed-effect model, we pooled dichotomous data with risk ratio (RR) and 95% confidence interval (CI) for analysis.
Results: In 5 trials involving 1120 patients with moderate to severe UC, targeting IL-23 showed significant superiority in inducing clinical remission [RR: 2.08, 95% CI, (1.66-2.61)], endoscopic remission [RR: 1.73, 95% CI, (1.39-2.16)], and histologic remission [RR: 1.88, 95% CI, (1.34-2.64)]. Additionally, individuals treated with IL-12/23p40 or IL-23p19 antagonists maintained clinical remission [RR: 1.85, 95% CI, (1.53-2.23)], endoscopic remission [RR: 2.03, 95% CI, (1.60-2.57)], and histologic remission [RR: 1.66, 95% CI, (1.11-2.48)]. Targeting IL-23 was linked with a reduced risk of any adverse events (AE) during both induction [RR: 0.94, 95% CI, (0.86-1.02)] and maintenance phases [RR: 0.93, 95% CI, (0.86-0.99)], any serious AE during the induction phase [RR: 0.53, 95% CI, (0.36-0.78)], and withdrawal due to AEs compared to patients receiving placebo during induction [RR: 0.24, 95% CI (0.14, 0.43)].
Conclusion: Targeting IL-23 demonstrates efficacy and safety for inducing and maintaining clinical and endoscopic remission in moderate-to-severe UC patients.
期刊介绍:
American Journal of Therapeutics is an indispensable resource for all prescribing physicians who want to access pharmacological developments in cardiology, infectious disease, oncology, anesthesiology, nephrology, toxicology, and psychotropics without having to sift through stacks of medical journals. The journal features original articles on the latest therapeutic approaches as well as critical articles on the drug approval process and therapeutic reviews covering pharmacokinetics, regulatory affairs, pediatric clinical pharmacology, hypertension, metabolism, and drug delivery systems.